Synergistic induction of miR-126 by hypoxia and HDAC inhibitors in cardiac myocytes

Huaping Shi, Lei Chen, Huilan Wang, Shoukang Zhu, Chunming Dong, Keith A. Webster, Jianqin Wei

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

HDAC inhibitors are under clinical development for the treatment of hypertrophic cardiomyopathy and heart failure although the mechanisms of protection are incompletely understood. Micro-RNA 126, an endothelium-specific miR has been assigned essential developmental roles in the heart by activating survival kinases ERK1/2 and Akt and increasing pro-angiogenic signaling. Here we provide the first evidence that hypoxia and HDAC inhibitors selectively and synergistically stimulate expression of miR-126 in cardiac myocytes. MiR-126 expression was increased 1.7-fold (p<. 0.05) after 1. h of hypoxic exposure and this was further enhanced to 3.0-fold (p<. 0.01) by simultaneously blocking HDAC with the pan-HDAC inhibitor Tricostatin A (TSA). TSA alone did not increase miR-126. In parallel, hypoxia and TSA synergistically increased p-ERK and p-Akt without effecting VEGF-A level. Knockdown of miR-126 with si-RNA eliminated inductions of p-ERK and p-Akt by hypoxia, whereas miR-126 overexpression mimicked hypoxia and amplified p-ERK and p-Akt in parallel with miR-126. The results suggest that miR-126 is a hypoxia-inducible target of HAT/HDAC and its activation in cardiac myocytes may contribute to cardioprotection by activating cell survival and pro-angiogenic pathways selectively during ischemia.

Original languageEnglish (US)
Pages (from-to)827-832
Number of pages6
JournalBiochemical and biophysical research communications
Volume430
Issue number2
DOIs
StatePublished - Jan 11 2013

Keywords

  • Cardiac myocytes
  • HDAC inhibitor
  • Hypoxia
  • Micro-RNA-126
  • Tricostatin A

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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